FDA Reviewers Raise No New Red Flags Over Lomitapide

FDA reviewers have raised no new concerns about lomitapide ahead of a Wednesday meeting of the Endocrinologic and Metabolic Drugs Advisory Committee.  The FDA today released briefing documents that evaluate the new drug application (NDA) for lomitapide capsules, the microsomal triglyceride transfer protein (MTP) inhibitor from  Aegerion Pharmaceuticals for use as an adjunct to a low-fat diet and other lipid-lowering drugs with or without LDL apheresis to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and triglycerides in patients with homozygous familial hypercholesterolemia. (On Thursday the same committee will meet to discuss a similar indication for Genzyme’s mipomersen injection. Briefing documents for that meeting will be released on Tuesday.)

The reviewers concluded that lomitapide was effective in lowering LDL cholesterol by about 40%. The drug also effectively reduced total cholesterol, apoB, triglyceride, non-HDL, VLDL, and Lp(a) levels. Lomitapide also lowered potentially beneficial HDL and Apo A1 levels. The reviewers said that “the clinical consequences, if any, of these changes are unknown.”

The committee will likely focus on side effects and safety issues related to lomitapide. Gastrointestinal side effects are common with the drug. More troubling are concerns about possible liver damage associated with the drug. In the pivotal trial 38% of the patients had ALT elevations greater than three times the upper limit of normal, and 24% had elevations five times the ULN. Most patients in the trials also had significant elevations in hepatic fat. The reviewers also noted that lomitapide might induce deficiencies in fat-soluble nutrients.

To address the safety issues related to lomitapide the FDA will ask the committee to evaluate a Risk Evaluation and Mitigation Strategies (REMS) that would limit access to the drug to medically appropriate patients and to provide education to prescribers about how to use lomitapide, how to prevent liver damage, and how to monitor patients during treatment. The REMS would  require special certification for health care professionals and pharmacies that prescribe and dispense the drug.

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  1. […] An FDA review raises a number of potentially significant safety concerns about the cholesterol-lowering drug mipomersen. The review appears ahead of a Thursday meeting of the Endocrinologic and Metabolic Drugs Advisory Committee to evaluate Genzyme’s new drug application (NDA) for use of the drug as an adjunct to maximally tolerated lipid-lowering medications and diet to reduce LDL, apolipoprotein B, total cholesterol, non-high density lipoprotein-cholesterol and lipoprotein (a) in patients with homozygous familial hypercholesterolemia (FH). Mipomersen is an antisense oligonucleotide inhibitor which targets apoB-100. (On Wednesday the same committee will meet to discuss a similar indication for lomitapide capsules, manufactured by Aegerion.) […]

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